L0301P96 - Fungal Infections
Fungi *eukaryotic obligate aerobes *ubiquitous in the environment *only a small number can cause human infection - 200 of 50,000 species *disease causing **ranging from mild to life threatening **majority are soil inhabitants *needs exogenous nutrients *capable of asexual and sexual reproduction *beneficial (metabolic capabilities) **food industry - bread, wine, cheese, beer **pharmaceuticals - production of antibiotics, enzymes, citric acid Basic Morphology *hyphae **septate (have septum) or non-septate *mycelium **mat of hyphae *yeast form **budding (3-5µm) *pseudomycelium **cells that line up to resemble a mycelium Classification #capable of sexual reproduction #presence of septate hyphae #shape of spore case *3 main classes: **dueteromycetes - asexual reproduction **oomycota - non-septate **eumycota - septate Comparison: Fungi vs Bacteria Fungal Diseases *fungal allergies *fungal toxicoses - mycotoxins *infections - mycosis **primary ***in a healthy individual **opportunistic ***in a person whose immune system is compromised in some way **cutaneous - most frequent **subcutaneous - under the skin surface Fungal Allergies Cause *exposure, generally inhalation, to fungal spores or mycelial cells Symptoms *type I allergy **vary from mild irritation to sudden death from anaphylactic shock *allergic bronchopulmonary mycoses *allergic sinusitis *hypersensitivity pneumonitis Diagnosis *patients history and tests Treatment *immunotherapy: repeated doses of an increasing doses of an allergen extract Fungal Toxins *generally secondary metabolites produced by the fungi *often have commercial importance *include: **antibiotics e.g. penicillin ***can be harmful to humans **mycotoxin **mushroom poison Mycotoxins *small molecules *produced by fungi growing in foods **such as grains, nuts or fruits *“poisoning by natural means” *causes mycotoxicoses: acute or chronic Symptoms *respiratory distress *burning sensation throat and lungs *teaches *memory loss *swollen lymph nodes *effect depends on: **type, amount and exposure **person’s age, health, sex, genetics, dietary status Example: Stachbotrys *grow on water damaged, cellulose-rich material in buildings **e.g. paper, ceiling tiles, wallpaper, etc *if inhaled, can cause: **dermatitis, memory loss, balance issues, cough, headache, pulmonary irritation, general malaise, seizures, and fever *treatment: **supportive care **removal of the fungi **activated charcoal Fungal Infections Cutaneous (superficial) Infections *caused by fungi that attack the skin or its appendages: **epidermis, hair, dead skin, nails *dermatomycoses **Tina ***also known as Ringworm ***caused by dermatophytes *sources: **human (direct or indirect contact) **animal **soil   Subcutaneous Infections *involve the dermis, subcutaneous tissues, muscle, fascia (fibrous tissue covering muscle or organ) *difficult to treat and may require surgical intervention *diseases **Sporotrichosis - forms ulcers and nodules **Chromoblastomycosis - longterm infection **Mycetoma   Opportunistic Infections *disease is most commonly seen in patients with defective immunity *can affect skin, mucosa, and internal organs   Examples Candida albicans *part of normal flora - yeast-like fungus *can cause oral or vaginal thrush, skin infections, endocarditis Cryptococcus neoformans *yeast *infection is slow **lung infection **meningoencephalitis *can be demonstrated in the CSF **characterised by large capsule *rapid identification by agglutination test Aspergillus fumigatus *causes aspergillosis *enters through the bronchial system, respiratory tract but also skin and mucosa *3 clinical types of pulmonary aspergillosis: **allergic ***hypersensitivity to the organism **aggressive tissue invasion ***primarily a pulmonary disease, but may disseminate to any organ **fungus ball ***mass in pre-existing lung cavities ***e.g. TB - lung scar or abscess *invasive aspergillosis is typically fatal in compromised patients Pneumocystos jiroveci (P. carinii) *causes pneumonia *high incidence in: **HIV patients **immunosuppressive therapy Antifungal Agents Targets *fungi are eukaryotes so comparatively difficult to develop drugs against them Drugs Polyenes *destroy membrane structure *include: **Amphotericin B ***used in systemic mycoses ***side effects **Nystatin ***topical use mucosal mycoses Azoles *disrupt ergosterol biosynthesis *fungistatic with GI side effects *include: **Fluconazole ***used for: surface and systemic mycoses, cryptococcal meningitis **Intraconazole ***used for cutaneous and systemic mycoses, aspergillosis Co-Trimoxazole *disrupt the synthetic pathway of tetrahydrofolic acid (THFA) *includes: **trimethoprim and sulfamethoxazole *used for the treatment of Pneumocystos jiroveci Antimetabolites *interfere with DNA synthesis *Flucytosine **administered orally **used in candidasis, cryptococcus **major side effects at high concentrations